Ph D Thesis - "Gr.T. Popa" Iasi

University of Medicine and Pharmacy „Gr. T. Popa” Iaşi
Dental Medicine Phaculty
Pharmacology Department
Head of Department: Prof. PhD. Mihai Nechifor
Variations of plasma and saliva
concentration of some bivalent cations in
pattients with oro-maxillo-facial area
pathology and their pharmacological
influences
Scientific coordinator,
Prof. phD. Mihai Nechifor
Ph D Thesis
IAŞI
– 2010 –
PhD Student,
Assit. Prof., MD, Elena Luca
1

General plan of the thesis
Thesis Synopsis
Introduction. Aims. Motivation for thesis theme election.
CURENT KNOWLEDGE STAGE IN THE FIELD
Chapter I
The role of bivalent cations in the human body and in the oro-maxillo-facial
area
I. Calcium
I. 1. Distribution in the human body
I. 2. Recommended daily intake and natural sources
I. 3. Elements of pharmacokinetics
I. 4. Roles in the human body
I. 5. Misbalances – pathology involvements
I. 6. Pharmacotherapy uses
II.. Magnezium
II. 1. Distribution in the human body
II. 2. Recommended daily intake and natural sources
II. 3. Elements of pharmacokinetics
II. 4. Roles in the human body
II. 5. Misbalances – pathology involvements
II. 6. Pharmacotherapy uses
III. Iron
III. 1. Distribution in the human body
III. 2. Recommended daily intake and natural sources
III. 3. Elements of pharmacokinetics
III. 4. Roles in the human body
III. 5. Misbalances – pathology involvements
III. 6. Pharmacotherapy uses
IV. Zinc
IV. 1. Distribution in the human body
IV. 2. Recommended daily intake and natural sources
IV. 3. Elements of pharmacokinetics
IV. 4. Roles in the human body
IV. 5. Misbalances – pathology involvements
IV. 6. Pharmacotherapy uses
V. Copper
V. 1. Distribution in the human body
V. 2. Recommended daily intake and natural sources
V. 3. Elements of pharmacokinetics
V. 4. Roles in the human body
V. 5. Misbalances – pathology involvements
V. 6. Pharmacotherapy uses
Chapter II
Main pathology groups of in the oro-maxillo-facial area
Chapter III
Main groups of therapeutic drugs used in the oro-maxillo-facial area
pathology
2

OWN CONTRIBUTIONS
Chapter I
Technics and methods used for the determinations of metallic ions
concentrations in biological fluids and tissues
Chapter II
Technics and methods udes for data statistical interpretation
Chapter III
Patients selection
Chapter IV
Sampling and primary prelucration of sampled biologic material (blood and
saliva) in patients and volunteers, in order to determine the concentration of
bivalent cations calcium, magnesium, iron, zinc, and copper
Chapter V
Research on variation of serum and saliva concentrations of some bivalent
cations (Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ ) suppurations of the oro-maxillo-facial area
I. Introduction
II. Aims
III. Subjects and method
IV. Results
V. Discutions
VI. Conclusion
Chapter VI
Research on variation of serum and saliva concentrations of some bivalent
cations (Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ ) chronic odontogenic maxillary sinusitis
I. Introduction
II. Aims
III. Subjects and method
IV. Results
V. Discutions
VI. Conclusion
Chapter VII
Research on variation of serum and saliva concentrations of some bivalent
cations (Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ ) malignant tumours of the oro-maxillo-facial
area
I. Introduction
II. Aims
III. Subjects and method
IV. Results
V. Discutions
VI. Conclusion
Chapter VIII
Research on variation of serum and saliva concentrations of some bivalent
cations (Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ ) benignant tumours of the oro-maxillo-facial
area
I. Introduction
II. Aims
III. Subjects and method
IV. Results
V. Discutions
VI. Conclusion
Chapter IX
3

Research on variation of serum and saliva concentrations of some bivalent
cations (Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ ) fractures of the oro-maxillo-facial area
I. Introduction
II. Aims
III. Subjects and method
IV. Results
V. Discutions
FINAL CONCLUSIONS
REFERENCES
Ph D Thesis Synopsis
I. Introduction. and motivation for thesis theme election.
Bivalent cations (Ca 2+ , Mg 2+ , Zn 2+ , Cu 2+ , Mn 2+ etc) play important roles in the
whole human and animal body.
Misbalances in intra and extra-cellular concentrations of these cations are involved
in the pathogenic mechamisms of numerous diseases.
The tough elements of the dento-maxillar apparatus, calcium and magnesium are
found in high concentrations. Calcium represent 37.9% of the enamel elements and
25.9% of dentin elements, while the maxilla bone contains 22.5% calcium. Magnesium
represents 0.42% of the enamel elements, 0.82% of dentin elements and 0.26% of
maxilla bone elements (Hallsworth A. S. et al., 1972). Manganese concentration is
higher in enamel than in dentin. Manganese concentration reaches its peak at the age of
approximately 12 in both genders, than it slowly decreases with aging. Thus, manganese
concentration in enamel was found to be 7.4±0.13 ppm at 10-12 years of age and it
decreases to 6.67±0.12 at the age of 25.
Appart from the structural role, which is particularely important for calcium and
magnesium, the mentioned ions, either macro-elements or trace elements, exercite
important functional roles, for example glandular secretion (saliva formation and
excretion is dependent on both calcium and zinc ions) (Liu X. et al., 2007). (Goto T. et
al., 2008). Zinc is found in secretory granules in the salivary gland. Zinc, together with
many zinc-dependent enzymes, is closely involved in the saliva production and
secretion, as well as in the contraction of the myoepithelial cells in the salivary glands.
There are about 300 zinc-dependent enzymes and other few hundreds are
magnesium-dependent for their activity. Zinc homeostasis is also important for the
protection against salivarz calculi formation. In subgingival calculus, zinc concentration
was found to be 5.4 times higher than in supragingival calculus. Homeostazia zincului
la nivel seric şi salivar are, rol în protecţia contra formării calculilor supragingivali
(Knuutilla M. et al., 1981; Knuutilla M. et al., 1979). Copper stimulates the activity of
dental osteoclasts.
Oral cavity tissues present a series of characteristics, some of which being
mentioned above:
- the permanent contact of the oral mucosa with both blood and saliva;
- direct contact with nor only to breath air, but also with food and ingested liquids;
- there are exposed to important mechanical solicitations during mastication;
- the presence of microbial commensal flora.
It also important to notice that different materials used in medical dental practice
contain important quantities of bivalent cations, mentioning that zinc oxide and calcium
hydroxide represent some of the most frequently used such materials.
4

Misbalances in the concentrations of numerous substances in the blood, including
cations, is also reflected in case of salivary concentrations, saliva being a very easy to
sample biological fluid.
Zinc deficiency, as well as the decreased zinc vs. copper concentrations ratio, has
been identified as a risk factor for the development of lots of infections, with different
localizing and etiological agent, as it determines immunity impairment. Yinc, as well as
copper, limits the adhesion of Porphyromonas gingivalis (but not Streptococcus oralis)
to periodontal structures, by favoring proteins adhesion to bacterial cell surface. The
fact could be speculated for prevention of periodontal disease, underlining the role of
different bivalent cations in the development of periodontal disease and generally in oral
infections (Tamura M. and Ochiai K., 2009). Zinc deficiency is also accompanied by
taste disturbances, salivary secretion disturbances, burning mouth syndrome.
Zinc deficiency, as well as decreased zinc vs. copper concentrations ratio, is also
considered a risk factor for malignant tumors development. In case of different types of
cancers, including oral cavity cancers, zinc concentration, al well as ratio between zinc
and copper serum concentration, is decreased. Oral neoplasm represent about 1 – 1.5%
of cancers developed in the human body. Considering the antagonism between copper
and zinc, including intestinal absorption antagonism, it is considered that zinc vs.
copper concentrations ratio is more important than concentration of yinc and copper
taken separately.
Several systemic diseases influence salivary concentration in different bivalent
cations. In this context, it has been showed that saliva from patients suffering from
diabetes mellitus, calcium concentration is significantly increased, while Zn 2+ and Mg 2+
concentrations are significantly decreased vs. normal gender and age match-controls.
In chronic rheumatoid arthritis in children, zinc salivary level is decreased
compared to normal age-paired controls (Una M. et al., 2004).
Also, bivalent cations are found in tooth constituting-elements, misbalances in
their concentrations being involved in tooth pathology. Magnesium is found in a greater
concentration in dentin compared to enamel (Hallsworth AS. et al., 1972).
A series of level found in tooth (and not only) such as hexokinase, are dependent
on magnesium for their proper activity. There are data suggesting that increased
magnesium tooth level is associated with increased carbohydrates consumption and may
be involved in tooth decay apparition. Okazaki M. et al., 2007, considers that both
magnesium and carbohydrates increase the solubility of apatite crystals and favours
tooth decay. By annualizing the composition of carietic milk teeth in comparison with
teeth without caries, Niedzielska K et al., 1990, found that carietic teeth contain more
manganese and copper, but less zinc compared to normal ones.
It is important to notice that both the individual cationic concentrations and the
ratio between their concentrations are important. Different cations concentration in teeth
is both age and gender-dependent and also the way their misbalances are involved in
teeth pathology is different at different ages.
Increased concentration of Mg 2+ in serum or other fluids was associated with
malignant tumours development (Varazashvili V.L.M. et al., 2006).
It is important to notice that both the individual cationic concentrations and the
ratio between their concentrations are important. Different cations concentration in
teeth is both age and gender-dependent and also the way their misbalances are involved
in teeth pathology is different at different ages.
II. The aim of this study is to investigate possible changes in the concentrations
of serum and saliva bivalent cations (Ca 2+ , Mg 2+ , Zn 2+ , Fe 2+ , Cu 2 ) in patients with
different pathology of the oro-maxillo-facial area:
5

- infections (suppurations of the oro-maxillo-facial area and chronic odontogenic
maxillary sinusitis);
- tumours oro-maxillo-facial area (both malignant and benignant);
- fractures of the oro-maxillo-facial area.
III. Patients and method. The studied group consisted in adult (minimum age
18) patients hospitalised in the oro-maxillo-facial clinic of “Sfântul Spiridon” Hospital
Iaşi, hospitalised between 2006 and 2008. Studies were performed in the conditions of
obtaining the necessary ethical authorisations and included patients have given their
informed consent.
The exclusion criteria for patients with suppurations of the oro-maxillo-facial
area, chronic odontogenic maxillary sinusitis benignant tumours of the oro-maxillofacial
area and fractures of the oro-maxillo-facial area, as well as for the corresponding
control group are the following:
• chronic diseases (diabetes mellitus, collagenoses, alcoholism, arterial
hypertension, cardiac failure, chronic or acute allergic diseases, chronic obstructive
pulmonary disease, liver cirrhosis, liver insufficiency, kidney failure, chronic allergic
diseases);
• patients to which medication containing Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ has
been administered within 2 weeks prior to recruiting, no matter the route;
• infectious pathology of any kind, either acute or chronic;
• acute allergic diseases;
• administration of diuretic medication within 2 weeks prior to recruiting, no
matter the route;
• administration of medication which modifies absorption, transport,
distribution, metabolism, elimination or balance of the studied cations within 2 weeks
prior to recruiting, no matter the route;
• pregnant or breastfeeding women;
• dehydrated or over-hydrated persons;
• malabsorption, malnutrition, diarrhoea or digestive transit impairment;
• surgical interventions within 6 weeks prior to the study;
• active bleeding into the oral cavity;
• malignant tumours, no matter the localisation;
• bone fractures 6 weeks prior to the study )apart from the main diagnosis in
case of fractures studied group);
• metallic prosthetic materials (any kind, any localisation).
In case of malignant tumours group, the presence of different pathologic
conditioned imposed that patients with arterial hypertension, collagenoses, infections,
either acute or chronic, allergic pathology, chronic obstructive pulmonary disease were
also included. A correspondent gender and age matched controlled, with similar
pathology, have been assigned as comparing controls for this group, being addes to the
control group used as reference to patients with suppurations of the oro-maxillo-facial
area, chronic odontogenic maxillary sinusitis benignant tumours of the oro-maxillofacial
area and fractures of the oro-maxillo-facial area.
Blood and saliva samples were collected before any therapeutic intervention or
diagnosis procedure, 12 hours after the last meal, between 7 00 and 9 00 A. M..
Blood samples were collected in biochemistry test-tubes with clotting accelerator
and centrifuges, within no more than 30 minutes after sampling, for 10 minutes at 4000
rotations per minute. Serum was separated and kept at -20ºC in simple test-tubes until
determination.
6

Saliva samples were collected by asking the volunteer to chew a cotton pad in the
form of a cylinder for 5 minutes. The pad was then introduced in a tube and
centrifuged. The supernatant was separated and kept at -20ºC in simple test-tubes until
determination.
Serum and salivary concentration of the studied cations (Ca 2+ , Mg 2+ , Zn 2+ , Fe 2+ ,
Cu 2 ) was performed by atomic absorption spectrofotometry. We have also assessed for
serum and saliva Ca 2+ /Mg 2+ and Zn 2+ / Cu 2+ concentrations ratio.
Data were statistically interpreted with ANOVA.
Number of volunteers
50
45
40
35
30
25
20
15
10
5
0
7
9
7
2
12
Control group 1
5 4 5
18 - 34 35 - 49 50 - 64 > 65 Total
9
Age (years)
Women Men Total
Fig. 1. Age and sex distribution diagram for control group 1 (reference for
patients diagnosed with suppurations of the oro-maxillo-facial area, chronic
odontogenic maxillary sinusitis benignant tumours of the oro-maxillo-facial area and
fractures of the oro-maxillo-facial area).
Number of volunteers
80
70
60
50
40
30
20
10
0
Control group 2
17 17
7
2
9 9 8
7
10
18 - 34 35 - 49 50 - 64 > 65 Total
Age (years)
Women Men Total
Fig. 2. Age and sex distribution diagram for control group 2 (reference for
patients diagnosed with malignant tumours of the oro-maxillo-facial area).
6
11
7
13
13
24
24
34
19
33
43
67
7

Number of volunteers
50
45
40
35
30
25
20
15
10
5
0
Suppurations group
13 13
8
10
7 6 7 6 7
2
4
18 - 34 35 - 49 50 - 64 > 65 Total
Age (years)
Women Men Total
Fig. 3. Age and sex distribution diagram for control diagnosed with suppurations
of the oro-maxillo-facial area.
Number of volunteers
25
20
15
10
5
0
4
2
6
Chronic odontogenic maxillary sinusitis group
7
4
3 3
2
11
5 5
3
2
18 - 34 35 - 49 50 - 64 > 65 Total
Age (years)
Women Men Total
Fig. 4. Age and sex distribution diagram for group 1 diagnosed with chronic
odontogenic maxillary sinusitis.
Number of volunteers
70
60
50
40
30
20
10
0
Malignant tumours group
18
15
11
6 8 7 8
7 7
2
18 - 34 35 - 49 50 - 64 > 65 Total
Age (years)
Women Men Total
16
23
26
12
27
21
11
37
47
23
64
8

Fig. 5. Age and sex distribution diagram for group diagnosed with malignant
tumours of the oro-maxillo-facial area.
Number of volunteers
25
20
15
10
5
0
1
2
3
5
Benignant tumours group
8
3 3 3
3
18 - 34 35 - 49 50 - 64 > 65 Total
6
Age (years)
Women Men Total
Fig. 6. Age and sex distribution diagram for group diagnosed with benignant
tumours of the oro-maxillo-facial area.
Number of volunteers
70
60
50
40
30
20
10
0
Fractures group
15 17 15
11 12 11 9
4 5 4 3
18 - 34 35 - 49 50 - 64 > 65 Total
Age (years)
Women Men Total
Fig. 7. Age and sex distribution diagram for group diagnosed with fractures of
the oro-maxillo-facial area.
IV. Results.
1. In case of patients with suppurations of the oro-maxillo-facial area,
compared to control healthy volunteers group, our study had found:
decreased serum zinc concentration (0.98±0.17 mg/L vs. 1.08±0.19mg/L,
p

increased saliva magnesium concentration (3.76±0.39 mg/L vs.
3.57±0.41mg/L, p

Fig. 10. Ratio between serum calcium concentration and serum magnesium
concentration in healthy control volunteers and in patients with suppurations of the oromaxillo-facial
area.
2
1,5
1
0,5
0
Ratio between serum zinc and copper
concentration
1,32±0,18
**
0,89±0,02
Control group
Patients with suppurations of the oro-maxillo-facial area
Fig. 11. Ratio between serum zinc concentration and serum copper concentration
in healthy control volunteers and in patients with suppurations of the oro-maxillo-facial
area.
mg / L
5
4
3
2
1
0
Saliva magnesium concentration
3,57±0,41
*
3,76±0,39
Control group
Patients with suppurations of the oro-maxillo-facial area
Fig. 12. Magnesium saliva concentration in healthy control volunteers and in
patients with suppurations of the oro-maxillo-facial area.
20
15
10
5
0
Ratio between saliva calcium and magnesium
concentration
15,45±2,42
*
14.53±2,41
Control group
Patients with suppurations of the oro-maxillo-facial area
11

Fig. 13. Ratio between saliva calcium concentration and saliva magnesium
concentration in healthy control volunteers and in patients with suppurations of the oromaxillo-facial
area.
Mg 2+ - saliva concentration (mg / L)
5
4,8
4,6
4,4
4,2
4
3,8
3,6
3,4
3,2
y = 0,1413x + 0,2568
R 2 = 0,5196
Correlation between serum and saliva magnesium in patients
3
20 22 24 26 28 30 32
Mg 2+ - serum concentration (mg / L)
Fig. 14. Correlation between serum and saliva magnesium in healthy control
volunteers and in patients with suppurations of the oro-maxillo-facial area.
Apart from iron serum concentration, which is lower in women (p

mg / L
30
25
20
15
10
5
0
Magnesium serum concentration
23,81±2,47
**
25,26±1,76
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 15. Magnesium serum concentration in healthy control volunteers and in
patients with chronic odontogenic maxillary sinusitis.
mg / L
1,20
1,00
0,80
0,60
0,40
0,20
0,00
Iron serum concentration
0,85±0,15
*
0,78±0,13
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 16. Iron serum concentration in healthy control volunteers and in patients
with chronic odontogenic maxillary sinusitis.
mg / L
1,00
0,80
0,60
0,40
0,20
0,00
Magnesium serum concentration
WOMEN
0,81±0,09
**
0,71±0,08
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 17. Iron serum concentration in healthy control volunteers women and in
women with chronic odontogenic maxillary sinusitis.
13

mg / L
1,5
1
0,5
0
Zinc serum concentration
1,08±0,19
**
0,95,19±0,17
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 18. Zinc serum concentration in healthy control volunteers and in patients
with chronic odontogenic maxillary sinusitis.
mg / L
5
4
3
2
1
0
Magnesium saliva concentration
3,57±0,41
*
3,76±0,38
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 19. Magnesium saliva concentration in healthy control volunteers and in
patients with chronic odontogenic maxillary sinusitis.
mg / L
0,4
0,3
0,2
0,1
0
Iron saliva concentration
0,30±0,04
*
0.28±0,07
Control group
Patients with chronic odontogenic maxillary sinusitis
Fig. 20. Iron saliva concentration in healthy control volunteers and in patients with
chronic odontogenic maxillary sinusitis.
14

20
10
0
Ratio between saliva calcium and magnesium
concentration
Control group
15,45±2,42
*
14,38±2,01
Patients with suppurations chronic odontogenic maxillary
sinusitis
Fig. 21. Ratio between saliva calcium concentration and saliva magnesium
concentration in healthy control volunteers and in patients with chronic odontogenic
maxillary sinusitis.
Mg 2+ - saliva concentration (mg / L)
5,00
4,80
4,60
4,40
4,20
4,00
3,80
3,60
3,40
3,20
Correlation between serum and saliva magnesium in patients
y = 0,1319x + 0,4322
R 2 = 0,3678
3,00
20,00 21,00 22,00 23,00 24,00 25,00 26,00 27,00 28,00 29,00 30,00
Mg 2+ - serum concentration (mg / L)
Fig. 22. Correlations between serum and saliva magnesium concentration in
healthy control volunteers and in patients with chronic odontogenic maxillary sinusitis .
Apart from iron serum concentration, which is lower in women (p

decreased serum zinc mass concentration versus serum copper mass
concentration ratio (1.20±0.40 vs. 1.37±0.48, p

mg / L
1,00
0,50
0,00
Control group
Magnesium serum concentraion
WOMEN
0,79±0,08
**
0,74±0,10
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 25. Iron serum concentration in control volunteers (women) and in patients
with malignant tumours of the oro-maxillo-facial area (women).
mg / L
1,5
1
0,5
0
Zinc serum concentraion
1,05±0,17
*
1,00±0,18
Control group
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 26. Zinc serum concentration in control volunteers and in patients with
malignant tumours of the oro-maxillo-facial area.
mg / L
1,2
1
0,8
0,6
0,4
0,2
0
Copper serum concentraion
0,82±0,18
*
0,88±0,21
Control group
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 27. Coper serum concentration in control volunteers and in patients with
malignant tumours of the oro-maxillo-facial area.
17

2
1,5
1
0,5
0
Ratio between serum zinc and copper
concentration
1,37±0,48
*
1,20±0,40
Control group
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 28. Ratio between saliva zinc concentration and copper magnesium
concentration in healthy control volunteers and in patients with malignant tumours of
the oro-maxillo-facial area.
mg / L
5
4
3
2
1
0
Magnesium saliva concentration
3,61±0,37
*
3,73±0,40
Control group
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 29. Magnesium saliva concentration in control volunteers and in patients with
malignant tumours of the oro-maxillo-facial area.
mg / L
0,8
0,6
0,4
0,2
0
Copper saliva concentration
0,61±0,07
*
0,63±0,06
Control group
Patients with malignant tumours of the oro-maxillo-facial area
Fig. 30. Copper saliva concentration in control volunteers and in patients with
malignant tumours of the oro-maxillo-facial area.
18

Cu 2+ - saliva concentration
(mg / L)
0,8
0,75
0,7
0,65
0,6
0,55
0,5
0,45
0,4
Correlation between serum and saliva magnesium in
patients y = 0,151x + 0,4638
R 2 = 0,4189
0,4 0,6 0,8 1 1,2 1,4 1,6 1,8
Cu 2+ - serum concentration (mg / L)
Fig. 31. Correlations between serum and saliva copper concentration in healthy
control volunteers and in patients with malignant tumours of the oro-maxillo-facial area.
Apart from iron serum concentration, which is lower in women (p

Some of the most evident signs liked to zinc deficiency are related to immune
system function impairment. As a result of immunodeficiency, the susceptibliity to viral
infectins, especially to viral infections, is increased. Zinc deficiency determines thymus
involution, impairment of delayed immune response, decreased T-cells in peripheral
blood, decreased proliferative response of T-cells to phytohemagglutinin, inhibition of
T-helper lymphocytes and natural-killer cells activity, as well as neutrophils functions
and antibodies (Walravens P. A. et al., 1979). Zinc deficiency is also associated with
decreased between T-helper 1 vs. T-helper 2 and decreased IFNγ production. From the
molecular point of view, apoptosis of T-cells line precursors is influenced by zinc ions
by expressions of Bcl-2/Bax genes, as zinc inhibits 3, 6, 7, and 8 caspases. In mature T
lymphocytes, zinc is necessary for stimulation of some enzymes such as C-proteinkinase
and tirosin-kinase C in the lymphocytes (LkC) (Hönscheid A. et al., 2009).
In both patients with oro-maxillo-facial area suppurative infections and patients
with chronic odontogenic maxillary sinusitis, decreases zinc serum level compared to
healthy volunteers controls (p

proven to be beneficial, as it normalizes the activity of cyclooxygenase-2 and reduces
cell proliferation rate.
Numerous other studies have identified changes in zinc, copper, or zinc vs. copper
concentration in serum, tissue or other biological fluids in patients with malignant
tumors:
o Varghese I. et al., 1987 have shown decreased Zn 2+ concentration, decreased
Cu 2+ concentration and decreased ration Zn 2+ /Cu 2+ in serum, in patients with
premalignant and malignant lesions of the oral cavity;
o Gupta S. K. et al., 2005 have shown decreased Zn 2+ , increased Cu 2+ and
decreased ration Zn 2+ /Cu 2+ in serum , in patients with carcinoma of the gallbladder;
o Błoniarz J. et al., 2003 a have shown decreased Zn 2+ , increased Cu 2+ in saliva
in patients with oral cancers;
o Akçil E. et al., 2004 have shown decreased plasma zinc concentration
(p

showed that Mg-dependent ATP-ase is involved in the development of some
microorganisms capable of invading the salivary glands. It is possible that increased
ratio between serum magnesium and calcium represents a predisposition factor to
bacterial suppurations of oro-maxillo-facial area. Moreover, magnesium is also
responsible for the expression of some Salmonella enterica genes (Lejona S. et al.,
2003).
There are also important data suggesting that magnesium excess is linked to
immune suppression:
Increased dietary magnesium intake suppreses some immune system functions
(decreases mytogenic response of lymphocytes to lipopolysaccharide, decreases
production of reactive oxygen species level by macrophages and nitrogen monoxide
production) (Son E. W. et al., 2007);
The intensity of inflammatory reaction, as non-specific immune response of
the body, is also impaired in case of increased extra-cell magnesium concentration
(Mazur A. et al., 2007).
In our study, both serum and saliva magnesium concentration was found increased
in patients with malignant tumors of the oro-maxillo-facial. The result is concordant
with some other researcher’s findings:
• Shpitzer T. et al., 2007, showed increased Mg 2+ saliva concentrations in
patients with oral carcinomas;
• Błoniarz J. et al., 2003, showed increased serum and saliva Mg 2+
concentrations, in patients with oral carcinomas;
• Grădinaru I. et al., 2008 showed increased serum and saliva Mg 2+
concentrations, in patients with parotid gland malignant tumors, II – III;
On the othe hand, Akçil E. et al., 2004 showed that there are no changes in
erythrocytes magnesium levels in laryngeal malignant tumors groups compared to
healthy volunteers.
There are also authors suggesting that magnesium deficiency may be a state
predisposing to malignant tumors development, as magnesium deficiency determines
endothelium and fibroblastic replicative senescence; Mildred et al., 1993 shows that in a
synthesis study referring to magnesium dietary deficiency and malignant tumors
development, but does not neglect apparently paradox data suggesting the contrarium.
Also, our research has revealed that, also there are no changes in saliva iron
concentration; there is a significant decrease in serum iron concentration in women with
malignant tumors of the oro-maxillo-facial area. However, we have not performed a
hematological complete evaluation for correlations indexes. We consider the finding
due to association of tumor anemia.
Błoniarz J. et al., 2003 shows increased saliva iron concentration in patients with
oral cancers, whreas serum iron is not chanced in patients with squamos carcinomas.
VI. Conclusions
1. In case of oro-maxillo-facial area suppurations, a moderate, but significant
increase in saliva magnesium concentration, as well as in magnesium vs. calcium
concentrations ratio in saliva has been determined, together with decreased serum zinc
concentration; these elements may be considered a marker for the development of a oral
suppuration;
2. There are no significant differences in the saliva and serum concentrations of
Ca 2+ , Mg 2+ , Zn 2+ , Fe 2+ and Cu 2+ in patients with fractures of the oro-maxillo-facial
territory;
22

3. There are no significant differences in the saliva and serum concentrations of
Ca 2+ , Mg 2+ , Zn 2+ , Fe 2+ and Cu 2+ in patients with benignant tumours of the oro-maxillofacial
area;
4. In case of patients with malignant tumours of the oro-maxillo-facial area, zinc
serum concentration is slightly, but significantly decreased, while saliva magnesium
concentration is slightly, but significantly increased;
5. In case of patients with chronic odontogenic maxillary sinusitis, serum and
saliva magnesium concentration is slightly, bust statistically significant, increased.
It may be possible that the ration between salivary calcium and magnesium
concentration, correlated with zinc serum decrease are involved in the development of
different pathological states of the oro-maxillo-facial area.
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